Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches

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Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches

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Title: Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches
Author: Pauthner, Matthias; Havenar-Daughton, Colin; Sok, Devin; Nkolola, Joseph P.; Bastidas, Raiza; Boopathy, Archana V.; Carnathan, Diane G.; Chandrashekar, Abishek; Cirelli, Kimberly M.; Cottrell, Christopher A.; Eroshkin, Alexey M.; Guenaga, Javier; Kaushik, Kirti; Kulp, Daniel W.; Liu, Jinyan; McCoy, Laura E.; Oom, Aaron L.; Ozorowski, Gabriel; Post, Kai W.; Sharma, Shailendra K.; Steichen, Jon M.; de Taeye, Steven W.; Tokatlian, Talar; Torrents de la Peña, Alba; Butera, Salvatore T.; LaBranche, Celia C.; Montefiori, David C.; Silvestri, Guido; Wilson, Ian A.; Irvine, Darrell J.; Sanders, Rogier W.; Schief, William R.; Ward, Andrew B.; Wyatt, Richard T.; Barouch, Dan H.; Crotty, Shane; Burton, Dennis R.

Note: Order does not necessarily reflect citation order of authors.

Citation: Pauthner, M., C. Havenar-Daughton, D. Sok, J. P. Nkolola, R. Bastidas, A. V. Boopathy, D. G. Carnathan, et al. 2017. “Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches.” Immunity 46 (6): 1073-1088.e6. doi:10.1016/j.immuni.2017.05.007. http://dx.doi.org/10.1016/j.immuni.2017.05.007.
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Abstract: Summary The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development. A bilateral, adjuvanted, subcutaneous immunization protocol induced reproducible tier 2 nAb responses after only two immunizations 8 weeks apart, and these were further enhanced by a third immunization with BG505 SOSIP trimer. We identified immunogens that minimized non-neutralizing V3 responses and demonstrated that continuous immunogen delivery could enhance nAb responses. nAb responses were strongly associated with germinal center reactions, as assessed by lymph node fine needle aspiration. This study provides a framework for preclinical and clinical vaccine studies targeting nAb elicitation.
Published Version: doi:10.1016/j.immuni.2017.05.007
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483234/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33490817
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